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Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT01393730
Recruitment Status : Completed
First Posted : July 13, 2011
Results First Posted : June 14, 2017
Last Update Posted : March 15, 2018
Sponsor:
Information provided by (Responsible Party):
Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Prostate Cancer
Interventions Drug: Abiraterone acetate
Drug: Dutasteride
Drug: Prednisone
Enrollment 40
Recruitment Details Patients enrolled from September 2011 through October 2012
Pre-assignment Details  
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

Period Title: Overall Study
Started 40
Treated 38
Evaluable AR Amplification 21
Evaluable AR Mutation 14
Completed 34
Not Completed 6
Reason Not Completed
Withdrawal by Subject             3
Other             2
Adverse Event             1
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

Overall Number of Baseline Participants 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 40 participants
61
(59 to 65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Female
0
   0.0%
Male
40
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 40 participants
40
1.Primary Outcome
Title Number of Participants With Androgen Receptor (AR) Related Mutations
Hide Description AR related mutation was defined as presence of T878A mutation. Expression of T878A was measured by established methods.
Time Frame Pairs of patients samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all patients evaluable for AR mutation.
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description:

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

Overall Number of Participants Analyzed 14
Measure Type: Count of Participants
Unit of Measure: Participants
1
   7.1%
2.Secondary Outcome
Title Change in Serum Levels of Testosterone
Hide Description Serum testosterone levels were estimated based on established methods. The change from baseline to progression was calculated for each participant.
Time Frame Samples for testosterone analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description:

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

Overall Number of Participants Analyzed 38
Median (Inter-Quartile Range)
Unit of Measure: ng/dL
0.25
(0.1 to 0.5)
3.Secondary Outcome
Title Prostate-Specific Antigen (PSA) Response
Hide Description PSA response was defined as decline of 50% from baseline confirmed by a PSA at least 4 weeks later based on Prostate-specific Antigen Working Group-2 (PSAWG-2) (2008) criteria.
Time Frame PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description:

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

Overall Number of Participants Analyzed 38
Measure Type: Count of Participants
Unit of Measure: Participants
34
  89.5%
4.Secondary Outcome
Title Time to PSA Progression
Hide Description Time to PSA progression based on the Kaplan-Meier method was defined as the time between registration and documented PSA progression. PSA progression based on Prostate-Specific Antigen Working Group-2 (PSAWG-2) (2008) criteria was an increase of >/=25% and >/= 2 ng/ml after 12 weeks for patients without a PSA decline from baseline and an increase of >/=25% and >/= 2 ng/ml above the nadir, confirmed by a 2nd value 3 weeks or later for patients with a PSA decline from baseline. PSA progression was reported not duration of response.
Time Frame PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description:

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

Overall Number of Participants Analyzed 38
Median (95% Confidence Interval)
Unit of Measure: months
5
(3 to 8)
5.Secondary Outcome
Title Best Overall Response
Hide Description Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time Frame Disease was evaluated radiologically at baseline and every 12 weeks cycles on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description:

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

Overall Number of Participants Analyzed 38
Measure Type: Count of Participants
Unit of Measure: Participants
6
  15.8%
6.Secondary Outcome
Title Time to Progression (TTP)
Hide Description TTP based on the Kaplan-Meier method is defined as the duration of time from study entry to documented first observation of progressive disease (PD). Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame Disease evaluation occurred every 12 weeks while patients were receiving treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description:

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

Overall Number of Participants Analyzed 38
Median (95% Confidence Interval)
Unit of Measure: Months
11
(8 to 15)
7.Secondary Outcome
Title Presence of AR Amplification
Hide Description Presence of AR amplification was measured by established methods.
Time Frame Patients' samples were evaluated at baseline and every 12 weeks on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all evaluable patients.
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description:

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

Overall Number of Participants Analyzed 21
Measure Type: Count of Participants
Unit of Measure: Participants
10
  47.6%
8.Secondary Outcome
Title Change in Serum Androgen Levels
Hide Description Serum androgen levels measured based on established methods. The change from baseline to progression was calculated for each participant.
Time Frame Pairs of patients' samples for androgen analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description:

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

Overall Number of Participants Analyzed 38
Median (Inter-Quartile Range)
Unit of Measure: ng/dl
1.2
(0.7 to 2)
9.Secondary Outcome
Title Change in Circulating Tumor Cells (CTCs) Levels
Hide Description CTCs were measured based on established methods.
Time Frame Pairs of patients' samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for this secondary endpoint.
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description:

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Adverse Event Reporting Description Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated. Patients appear once for a given toxicity type. Serious and Other Adverse Events (AEs) were defined as events of grades 3-5 and grades 1-2, respectively, based on Common Terminology Criteria for Adverse Events version 4 (CTCAEv4). 'Other’ events have no further specification.
 
Arm/Group Title Abiraterone + Prednisone + Dutasteride
Hide Arm/Group Description

Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression

Abiraterone acetate: 1000 mg orally, once per day

Dutasteride: 3.5 mg orally once per day

Prednisone: 5 mg orally once per day

All-Cause Mortality
Abiraterone + Prednisone + Dutasteride
Affected / at Risk (%)
Total   0/38 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Abiraterone + Prednisone + Dutasteride
Affected / at Risk (%)
Total   12/38 (31.58%) 
Cardiac disorders   
Conduction abnormality/Atrioventricular heart block - AV block-second degree Mobitz Type II  1  1/38 (2.63%) 
Cardiac disorders - Other, specify  1  1/38 (2.63%) 
Infections and infestations   
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Ureter  1  1/38 (2.63%) 
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Vagina  1  1/38 (2.63%) 
Injury, poisoning and procedural complications   
Thrombosis/embolism (vascular access-related)  1  5/38 (13.16%) 
Thromboembolic event  1  1/38 (2.63%) 
Investigations   
Alanine aminotransferase increased  1  1/38 (2.63%) 
Lipase increased  1  1/38 (2.63%) 
Lipase  1  1/38 (2.63%) 
Musculoskeletal and connective tissue disorders   
Bone: spine-scoliosis  1  2/38 (5.26%) 
Nervous system disorders   
"Neuropathy: cranial - CN III Pupil, upper eyelid, extra ocular movements"  1  1/38 (2.63%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Abiraterone + Prednisone + Dutasteride
Affected / at Risk (%)
Total   38/38 (100.00%) 
Blood and lymphatic system disorders   
Bone marrow cellularity  1  2/38 (5.26%) 
Lymphopenia  1  1/38 (2.63%) 
Blood/Bone Marrow-Other (Specify)  1  1/38 (2.63%) 
Cardiac disorders   
Conduction abnormality/Atrioventricular heart block - Wolff-Parkinson-White syndrome  1  2/38 (5.26%) 
Palpitations  1  1/38 (2.63%) 
Cardiac disorders - Other, specify  1  1/38 (2.63%) 
Congenital, familial and genetic disorders   
Congenital, familial and genetic disorders  1  1/38 (2.63%) 
Ear and labyrinth disorders   
External ear pain  1  1/38 (2.63%) 
Tinnitus  1  1/38 (2.63%) 
Ear and labyrinth disorders  1  1/38 (2.63%) 
Eye disorders   
Cataract  1  2/38 (5.26%) 
Eye disorders - Other, specify  1  1/38 (2.63%) 
Gastrointestinal disorders   
Abdominal pain  1  2/38 (5.26%) 
"Fistula, GI - Anus"  1  1/38 (2.63%) 
"Fistula, GI - Esophagus"  1  7/38 (18.42%) 
"Fistula, GI - Ileum"  1  4/38 (10.53%) 
"Fistula, GI - Jejunum"  1  2/38 (5.26%) 
"Fistula, GI - Stomach"  1  1/38 (2.63%) 
Nausea  1  6/38 (15.79%) 
"Obstruction, GI - Esophagus"  1  1/38 (2.63%) 
"Stricture/stenosis (including anastomotic), GI - Duodenum"  1  5/38 (13.16%) 
Gastrointestinal disorders - Other, specify  1  1/38 (2.63%) 
General disorders   
"Fatigue (asthenia, lethargy, malaise)"  1  1/38 (2.63%) 
Obesity  1  1/38 (2.63%) 
Sweating (diaphoresis)  1  22/38 (57.89%) 
Weight gain  1  3/38 (7.89%) 
Weight loss  1  3/38 (7.89%) 
Localized edema  1  1/38 (2.63%) 
Non-cardiac chest pain  1  1/38 (2.63%) 
Pain  1  8/38 (21.05%) 
General disorders and administration site conditions - Other, specify  1  1/38 (2.63%) 
Infections and infestations   
Infection (documented clinically/microbiologically) w/Grade 3/4 neutrophils -Brain  1  2/38 (5.26%) 
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Liver  1  1/38 (2.63%) 
Infection (documented clinically or microbiologically) w/Grade 3 or 4 neutrophils -Nerve-peripheral  1  1/38 (2.63%) 
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Peristomal  1  1/38 (2.63%) 
Skin infection  1  2/38 (5.26%) 
Infection (documented clinically/microbiologically) w/Grade 3/4 neutrophils -Upper aerodigestive NOS  1  1/38 (2.63%) 
Urinary tract infection  1  2/38 (5.26%) 
Injury, poisoning and procedural complications   
Bruising  1  2/38 (5.26%) 
Injury, poisoning and procedural complications  1  2/38 (5.26%) 
Fracture  1  1/38 (2.63%) 
Injury, poisoning and procedural complications - Other, specify  1  1/38 (2.63%) 
Investigations   
Alanine aminotransferase increased  1  7/38 (18.42%) 
Alkaline phosphatase increased  1  1/38 (2.63%) 
Aspartate aminotransferase increased  1  8/38 (21.05%) 
Blood bilirubin increased  1  4/38 (10.53%) 
Metabolism and nutrition disorders   
Anorexia  1  3/38 (7.89%) 
"Bicarbonate, serum-low"  1  6/38 (15.79%) 
Hypocalcemia  1  1/38 (2.63%) 
"Glucose, serum-high (hyperglycemia)"  1  12/38 (31.58%) 
Musculoskeletal and connective tissue disorders   
Bone: spine-scoliosis  1  3/38 (7.89%) 
Extremity-lower (gait/walking)  1  7/38 (18.42%) 
Extremity-upper (function)  1  5/38 (13.16%) 
Fibrosis-cosmesis  1  1/38 (2.63%) 
Fracture  1  1/38 (2.63%) 
Local complication - device/prosthesis-related  1  2/38 (5.26%) 
"Muscle weakness, generalized or specific area (not due to neuropathy) - Extremity-upper"  1  2/38 (5.26%) 
Osteoporosis  1  4/38 (10.53%) 
Soft tissue necrosis - Abdomen  1  1/38 (2.63%) 
Soft tissue necrosis - Head  1  1/38 (2.63%) 
Soft tissue necrosis - Neck  1  4/38 (10.53%) 
Musculoskeletal/Soft Tissue-Other (Specify)  1  2/38 (5.26%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify  1  1/38 (2.63%) 
Nervous system disorders   
Irritability (children <3 years of age)  1  1/38 (2.63%) 
"Leak, cerebrospinal fluid (CSF)"  1  2/38 (5.26%) 
"Neuropathy: cranial - CN III Pupil, upper eyelid, extra ocular movements"  1  2/38 (5.26%) 
Nervous system disorders  1  1/38 (2.63%) 
Nervous system disorders - Other, specify  1  2/38 (5.26%) 
Psychiatric disorders   
Insomnia  1  4/38 (10.53%) 
Psychiatric disorders  1  1/38 (2.63%) 
Renal and urinary disorders   
"Leak (including anastomotic), GU - Kidney"  1  4/38 (10.53%) 
"Leak (including anastomotic), GU - Spermatic cord"  1  2/38 (5.26%) 
"Leak (including anastomotic), GU - Ureter"  1  1/38 (2.63%) 
Renal and urinary disorders - Other, specify  1  1/38 (2.63%) 
Reproductive system and breast disorders   
Gynecomastia  1  2/38 (5.26%) 
Testicular pain  1  1/38 (2.63%) 
Respiratory, thoracic and mediastinal disorders   
Atelectasis  1  1/38 (2.63%) 
Cough  1  3/38 (7.89%) 
Dyspnea  1  3/38 (7.89%) 
Laryngeal fistula  1  1/38 (2.63%) 
Prolonged intubation after pulmonary resection (>24 hrs after surgery)  1  3/38 (7.89%) 
Pneumothorax  1  1/38 (2.63%) 
Respiratory, thoracic and mediastinal disorders  1  1/38 (2.63%) 
Respiratory, thoracic and mediastinal disorders - Other, specify  1  2/38 (5.26%) 
Skin and subcutaneous tissue disorders   
Burn  1  1/38 (2.63%) 
Hyperpigmentation  1  1/38 (2.63%) 
Nail changes  1  1/38 (2.63%) 
Rash: dermatitis associated with radiation - Chemoradiation  1  1/38 (2.63%) 
Skin breakdown/decubitus ulcer  1  3/38 (7.89%) 
Striae  1  2/38 (5.26%) 
Ulceration  1  1/38 (2.63%) 
Dermatology/Skin-Other (Specify)  1  4/38 (10.53%) 
Surgical and medical procedures   
Intra-operative injury - Pharynx  1  1/38 (2.63%) 
Vascular disorders   
Phlebitis (including superficial thrombosis)  1  2/38 (5.26%) 
Portal vein flow  1  10/38 (26.32%) 
Thrombosis/embolism (vascular access-related)  1  15/38 (39.47%) 
Thrombosis/thrombus/embolism  1  2/38 (5.26%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Mary-Ellen Taplin
Organization: Dana-Farber Cancer Institute
Phone: 617-582-7221
Responsible Party: Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01393730     History of Changes
Other Study ID Numbers: 10-448
First Submitted: June 21, 2011
First Posted: July 13, 2011
Results First Submitted: March 17, 2017
Results First Posted: June 14, 2017
Last Update Posted: March 15, 2018